Pain is one of the most common, yet difficult to manage, clinical problems that physicians face. It is well known that pain is a stressful experience. However, pain clearly is perceived differently from non- nociceptive stressors. This proposal approaches the interface between stress and nociception in rodents with the following goals: 1) to explore the neuronal substrates that may give nociceptive stimuli their uniquely aversive qualities, 2) to determine how stress modulates neuronal responses to noxious stimulation, and 3) to correlate changes in pain behavior caused by narcotics with changes in neuronal activation at the supraspinal level, in order to identify specific brain areas that may be responsible for narcotic.induced alterations in response to nociception. We propose to accomplish these goals by correlating behavioral changes observed after different types of nociceptive and stressful stimulation with patterns of immediate early gene (IEG) expression induced by these stimuli. These patterns will be mapped using in situ hybridization. Both noxious and stressful stimuli have been shown to induce changes in IEG expression in relevant neuronal systems. However, most work in nociceptive IEG activation has focused on the spinal cord. Few studies have examined the supraspinal components of this response, and this work has typically been done in anesthetized animals. We propose a series of logically progressing studies designed to answer the following questions: 1) Do nociceptive and non-nociceptive stressors activate distinct neuronal systems? 2) What changes in IEG activation patterns occur during chronic nociceptive states, and how docs chronic exposure to nociceptors affect responses to acute nociceptive stimuli? 3) Does the stress history of an animal alter neuronal responses to acute nociceptive stimuli? 4) What are the effects of narcotics on pain behavior and supraspinal IEG activation when administered before or after nociceptive stimulation? We hope this information will improve the understanding of the basic mechanisms underlying aversive and affective responses to pain, and possibly lead to therapies that could help alleviate the suffering associated with pain in man.